Over the last decade, we have seen remarkable progress in our ability to characterize disease and develop novel targeted therapies that turn otherwise untreatable diseases into chronic and sometimes curable conditions. Oncology has led the way with the development of many drugs that target particular mutations in the DNA of tumors. In addition, we have seen real success with genetically targeted novel therapeutics in other areas such as Cystic Fibrosis, Batten’s Disease, Spinal Muscular Atrophy among other rare diseases.
This revolution in drug development has been driven by continuous improvements in diagnostic technology. Genomics, transcriptomics, immune cell characterization and other types of testing enable deeper evaluation of the mechanisms of disease, more accurate diagnosis of patients, and better stratification of patients into relevant genetically-defined disease sub-cohorts for treatment (even cohorts as small as a single patient-truly an N-of-One) . Based on the testing and resulting insights into disease mechanisms, the life science industry has been able to design an increasing number of therapies that target specific molecular alterations. Success with small cohorts can be translated to other disease areas and larger populations of patients.
In oncology, for example, Burris et. al. showed that as many as 37% of the patients who received broad-based NGS testing have at least one clinically relevant mutation. Even for rarer cancers, diagnostic testing can drive care. In a study of 200 patients with cancer of unknown primary, almost all had at least one clinically relevant molecular alteration. 83% of the biliary cancers have clinically relevant genomic alterations. Markers like NTRK and TMB predict drug sensitivity to NTRK and checkpoint inhibitors, respectively, regardless of the tumor histology!
Despite this progress in technology, it is still challenging for patients and physicians to get access to the knowledge needed to take advantage of these novel therapeutics. Many physicians are still only using it for refractory cancer patients if at all.,
This is not just true in cancer. There are over 7000 rare diseases with an estimate of over 300 million people living with a rare disease globally, about 10% of these live in the US. It is estimated that 72% of these diseases are genetic and 70% of these diseases begin in children. It takes about 6-8 years from symptom onset to diagnosis and patients are evaluated by an average of 7.3 physicians before a diagnosis is made. Delays in diagnosis and treatment are extremely costly and associated with significant morbidity and distress. An NHS study of rare disease showed a dramatically higher cost for rare disease patients than others over a 10 year period due to hospitalizations and diagnostic procedures. The use of next-generation sequencing testing can shorten the time to diagnosis, and can provide the data needed by the life science industry to design therapies that target many of these rare and difficult to diagnose diseases.
Diagnostic testing is the key to the treatment for so many patients. In addition to genomics, there is greater recognition that many other types of molecular data are important for guiding drug development and treatment of individual patients. The complexity of this data will create ongoing challenges for physicians and patients. Technologies for the identification of digital biomarkers will create yet another way for understanding patients, but further increase the complexity of analysis required to assess the benefit of a particular therapy. Thus, new frameworks, platforms, and tools for analysis that enable the application and integration of diagnostic data across disease areas will be critical for empowering physicians to use the data for the benefit of their patients. Up to date data on outcomes and cost are essential for demonstrating value to payors. The time is now—patients cannot wait!
Join Jennifer and other industry leaders as they further this discussion at MassBio’s State of Possible Conference, taking place virtually on August 26-27.
About the Author
Jennifer Levin Carter MD, MPH, MBA
JLC Precision Health Strategies, LLC
Jennifer Levin Carter, MD, MPH, MBA is a healthcare executive, Board member and entrepreneur with a successful track record of developing innovative strategies and solutions at the intersection of and healthcare IT and services, digital health and machine learning, precision medicine, genomics and its application to healthcare delivery and life sciences including novel clinical trial delivery and drug development. Dr. Carter has a passion for finding solutions to improve patient care with deep expertise in creation and implementation of systems and platforms using data and technology to support patient and physician access to improved therapeutic strategies. She was most recently, VP and of Head of Precision Health at Integral Health, A Flagship Pioneering company. In 2018, She Founded TrialzOWN, Inc. a novel clinical trials company in stealth, and was CEO until it’s prelaunch acquisition by Integral Health in March, 2019. Prior to TrialzOWN, Dr. Carter was the Founder and President of N-of-One®, Inc. She served at CEO from 2008-2012, and Chief Medical Officer from 2012 until its acquisition by Qiagen (Market Cap $8B) in 2019. At N-of-One, Dr. Carter led the creation of award winning solutions that delivered novel treatment strategies to hundreds of thousands of patients with cancer globally.
 Burris, H. et.al. Assessing the Value of Next-Generation Sequencing Tests in a Dynamic Environment. ASCO.Org/edbook 2018 ASCO Educational Book.
 Lee, H and Jeffrey Ross. The Potential Role of Comprehensive genomic profiling to guide targeted therapy for patients with biliary cancer. Ther. Adv. Gastroenterol. 2017, Vol 10 (6) 507-520.
 Hegert, Jessica. Review reveals challenges of NGS Testing in Community Practices, Proactive Measures to Increase Utility. OcLive, June 3, 2020.
 Fact Sheet: What is Community Oncology. 2017
 It takes too long for rare disease to be diagnosed. Here’s how that can change. World Economic Forum
 The Global Challenge of Rare Disease Diagnosis: The Benefits of an improved diagnosis journey for patients. Shire.
 Imperial College Health Partners: A preliminary assessment of the potential impact of rare diseases on the NHS. Mendelian. Report on intial findings, 2018.